Research Information System
Brain and Development, vol.48, no.2, 2026 (SCI-Expanded, Scopus)
Background: Senescence, a steady loss of proliferative capacity triggered by complex pathways, has received attention in neurodegenerative diseases but remains obscure in epilepsy. This study aims to investigate whether the stress of frequent seizures in children triggers cellular senescence. Methods: Peripheral blood mononuclear cells (PBMC) from children under 12 years of age were analyzed for senescence-associated β-galactosidase (SA-βgal) activity, telomere length, expression of cell cycle arrest genes [p53, p16, p21, retinoblastoma (RB)] along with telomerase reverse transcriptase (TERT), insulin-like growth factors (IGF), and interleukin-6 (IL-6)/tumor necrosis factor-alpha (TNF-alpha) levels. We compared these markers in drug-resistant epilepsy patients with malformations of cortical development (MCD) to those in drug-responsive epilepsy patients and healthy controls (n = 10 each). Results: Our study showed similar PBMC SA-βgal levels across all groups. CD8+ T cell subgroup analysis from the drug-resistant epilepsy group exhibited higher SA-βgal activity. Drug-resistant epilepsy group was associated with the longest telomeres and high TERT expression. p53 and RB expressions were similar to healthy controls in drug-resistant epilepsy group, whereas p21 and p16 expressions were higher. Children with drug-resistant epilepsy with MCD showed significantly higher levels of IL-6 and TNF-alpha than healthy controls or children with drug-responsive epilepsy. Conclusion: We observed no evidence of established stress-induced premature or replicative senescence in drug-resistant epilepsy patients. However, elevated proinflammatory cytokines and high p21/p16 expression in the drug-resistant group may suggest ongoing seizures cause cellular stress which could increase susceptibility to senescence in drug-resistant pediatric epilepsy patients over time.